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Investigating febrile UTI in infants: Is a cystogram necessary?
Journal of Pediatric Urology (2010) 6, 148e152
Investigating febrile UTI in infants: Is a cystogram necessary? G. Soccorso a, J. Wagstaff a, K. Blakey a, G.D. Moss b, P. Broadley c, J.P. Roberts a, P. Godbole a,* a
Department of Paediatric Urology, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK Department of Medicine, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK c Department of Radiology, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK b
Received 22 March 2009; accepted 16 June 2009 Available online 19 July 2009
KEYWORDS Infantile UTI; VUR; MCUG; DMSA
Abstract Objective: Current imaging recommendations for investigating any infantile febrile urinary tract infection (UTI) are ultrasound scan (US), micturating cystourethrogram (MCUG) and dimercaptosuccinic acid (DMSA) scan. The aim of this retrospective cohort study was to determine the need and indications for MCUG in the investigation of a first febrile infantile UTI, as doubts have been raised over its benefit. Patients and methods: Information on 427 infants who had undergone US, MCUG and DMSA following a first febrile UTI was prospectively recorded. The infants were divided into two groups: A (354) with normal renal US and B (73) with abnormal US. DMSA findings were correlated with findings on MCUG. Main outcome measures were incidence of recurrent UTIs, change in management or intervention as a result of MCUG, and outcome at discharge. Results: Only 21/354 (6%) infants in Group A had both scarring on DMSA and vesicoureteric reflux (VUR), predominantly low-grade on MCUG. In Group B (abnormal US), 23/73 (32%) had scarring on DMSA and vesicoureteric reflux, predominantly high grade on MCUG. Of the infants with non-scarred kidneys, 73% had dilating reflux. Successful conservative treatment was performed in 423 infants, and 4 infants in Group B required surgery. Conclusion: We recommend US and DMSA in all infantile febrile UTI cases. Where US is normal, MCUG should be reserved for those cases with abnormal DMSA. Where US is abnormal, MCUG should be performed irrespective of findings on DMSA scan. A randomized prospective study is necessary to evaluate this further. ª 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction
* Corresponding author. E-mail address: [email protected] (P. Godbole).
Febrile UTI is a common problem seen by paediatricians, the urinary tract being the second most common site of infection in infants and children after the respiratory tract.
1477-5131/$36 ª 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2009.06.009
Febrile UTI in infants Diagnosis and treatment of UTI are particularly important in infants, given the long-term associations, such as renal scarring, hypertension, chronic renal failure and problems associated with pregnancy [1e3]. Imaging protocols in an infant with a first febrile UTI continue to be a subject of debate. The current practice guidelines of the Royal College of Physicians of London (1991) [4] and of the American Academy of Pediatrics (AAP) (1999) [5] recommend renal US during the acute phase, MCUG several weeks after the infection to identify VUR or obstructive lesions, and a renal DMSA scan at a minimum of 3 months after the infection to rule out renal scarring. The role of MCUG is controversial. Several authors have raised doubts over the benefit of an MCUG in the investigation of a first UTI in children aged less than 1 year of age [6e8]. In the UK, The National Institute of Clinical Excellence (NICE) produced recent guidelines to improve and make more cost effective the diagnosis, treatment and further management of UTI in childhood [9]. The recommendations are complex, dividing children into different age groups and UTIs into different variants, combinations of which determine the type and timing of subsequent imaging studies. We conducted a 10-year retrospective review of infants presenting with a febrile pyelonephritic illness to a tertiary paediatric hospital to specifically investigate the role of MCUG in these infants. Analysing our data, we suggest a diagnostic protocol correlating it with the recent NICE guidelines.
Methods All infants under 1 year of age presenting with a febrile UTI were admitted under the care of paediatricians. At our institution, the current practice is for all infants presenting with a febrile UTI to be admitted for intravenous antibiotics with subsequent chemoprophylaxis till investigations are complete. These infants have an ultrasound (US) scan during this admission. Subsequently, all infants have an MCUG and DMSA scan, the DMSA scan being at least 3 months following the last infection. Where the acute US scan shows evidence of bladder outlet obstruction, this is confirmed by MCUG and managed accordingly. Those infants under 1 year of age referred by their primary care practitioner with a history of a febrile UTI are investigated along the same lines with US, MCUG and DMSA. The imaging data for these infants was prospectively recorded on a radiology database. Case notes of all infants from the database between 1996 and 2006 were available for review. A febrile UTI was defined as pyrexia >38 C associated with culture-proven pure growth of an organism (>105 colony-forming units/high-power field) from an appropriately collected urine sample. The sample was collected as a clean-catch midstream urine sample. Where this was not possible, a suprapubic aspirate with US control was utilized to obtain a sample. The US examination was considered normal in the case of bilateral normal kidneys, with no evidence of hydroureteronephrosis or bladder abnormality. The VUR on MCUG was graded according to the international VUR classification [10]. DMSA was considered normal if uptake of radioisotope was homogenous with no evidence of scarring and relative uptake within normal range.
149 Six paediatric radiologists reported individual imaging studies and were blinded to the reports of other studies for the same infant. A total of 427 infants, 258 boys (60%) and 169 girls (40%) with a median age of 5.2 months (0e12) were eligible for enrolment. The infants were divided in two groups: normal renal US (Group A Z 354 infants/708 renal units) and abnormal US (Group B Z 73 infants/146 renal units). For both groups, DMSA findings were correlated with findings on MCUG. Main outcome measures evaluated were incidence of recurrent UTIs, change in management or intervention as a result of the MCUG, and outcome at discharge. Institutional ethics and clinical effectiveness committee approval was obtained for this study.
Results All infants had a proven febrile UTI: the most common organism isolated was Escherichia coli (67%) followed by Enterobacter (21%) and Enterococcus (8%). Klebsiella was isolated from 3.5% of the infants and Staphylococcus aureus in only 0.5%.
Group A: normal US In Group A (Fig. 1) (n Z 354), there were 142 girls (40%) and 212 boys (60%). The average age was 4.5 months (range 0.3e12 months). Scarring on DMSA scan was found in 38/354 (11%). Of these, 21/38 (55%) had VUR on MCUG. Hence, 21/ 354 (6%) infants had both VUR and scarring on DMSA. The VUR was predominantly low grade. Of the 354 infants, 316 (89%) had a normal DMSA scan. Of these, 48/316 (15%) had low-grade VUR on MCUG. Overall, VUR was present in 69 infants (19%): 38 were male and 31 female; VUR was predominantly of low grade, unilateral in 37 and bilateral in 32 infants, making a total of 101 refluxing renal units. All infants of Group A were successfully treated conservatively by the medical team with prophylactic antibiotics, regular follow up and renal function/blood pressure monitoring as indicated. Those with normal investigations were discharged and chemoprophylaxis was discontinued. There was no further occurrence of UTI in infants in Group A during the period of observation. All were normotensive at discharge and on no medication.
Group B: normal US Seventy-three infants (Fig. 2) (average age 3.9 months, range 0.2e12 months), 46 boys (63%) and 27 girls (37%), showed abnormal findings on US. In 27 cases (37%) both renal units were abnormal. The most common findings were moderate to severe hydroureteronephrosis and duplex system. Forty-three infants (59%) revealed scarring on DMSA scan and 23/43 (53%) demonstrated VUR on MCUG. The majority of infants (73%) without scarring on DMSA scan showed VUR on cystogram. Overall, VUR was present in 45/73 infants (62%), 29 male and 16 female, for a total of 66 renal units, and was grade IIeV. Of the 73 infants with an abnormal US, 23 had scarring on DMSA and VUR on MCUG (32%).
150
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Fig. 1
Group A: results of imaging studies.
The same conservative strategy (monitoring and prophylaxis) used for Group A was applied successfully by the medical team in the majority of the children of Group B. Breakthrough UTI rate was 12% (9/73). Eight children presented with one episode of cystitis. Only one child presented with further pyelonephritis. These episodes were diagnosed on clinical and radiological grounds. All nine continued with the conservative treatment. Infants with VUR or scars on DMSA continued on prophylaxis until they were potty trained, and remained under appropriate follow up for monitoring of blood pressure and renal function where indicated. Only four children in Group B (5%) required surgical intervention (Table 1). Patients 1 and 4 had a right heminephrectomy and right nephrectomy, respectively, for a non-functioning upper moiety of a right duplex (Patient 1) and a poorly functioning kidney (Patient 4). Patients 2 and 3 had bilateral ureteric reimplantation in view of their recurrent episodes of urinary sepsis.
Discussion In this study, we reviewed our practice with the aim of simplifying the routine imaging protocols for infantile UTI suggested by the Royal College of Physicians and the AAP. Their recommendations are not based on firm evidence [11].
Fig. 2
The authors appreciate that the AAP 1999 guidelines recommend imaging for infants between the age of 2 months and 2 years. However, in our institute, the Royal College of Physicians guidelines 1991 have been followed and this study is based on infants treated accordingly. US is the routine, simple, non-invasive method of investigation for a child with UTI. Modern US is very sensitive in the assessment of the gross anatomy of the urinary tract, demonstrating dilatation of ureters, hydronephrosis, renal shapes, duplications, ureteroceles, and horseshoe kidney. In our study, US showing dilatation of the urinary tract correlated well with VUR grade IIIeV on MCUG. This was particularly evident in the infants of Group B; 19% of the infants in Group A had reflux but this was mainly nondilating on cystogram and none was of grade IV or V. As previously reported in other studies, we found a poor correlation between VUR demonstrated on MCUG and renal scarring on DMSA; in fact, 45% of infants with scarred kidneys in Group A and 47% in Group B did not show reflux on cystogram. This could be explained by the fact that reflux is often intermittent or that it is not a prerequisite for renal damage [12,13]. It has been suggested that MCUG contributes little to the management of infantile UTI in the context of normal US and DMSA [7]. In Group A the majority of infants (76%) with
Group B: results of imaging studies.
Febrile UTI in infants Table 1
151
Patients from Group B who required surgical treatment.
No.
US
MCUG
DMSA
Surgery
1
Right duplex with hydronephrosis and ureterocele Right hydroureteronephrosis with right scarring Bilateral hydroureteronephrosis with hypertrophic bladder Right hydroureter Left hydronephrosis
Right GIII VUR Ureterocele
Right duplex with non-functioning upper pole Left lower pole scar Bilateral scarring
Right heminephrectomy
2 3 4
Bilateral VUR Right GIV Left GIII ***Bilateral VUR Right GV Left GIII Bilateral GIII VUR
Bilateral scarring Function right kidney 6% Left lower pole scar
STING unsuccessful Bilateral ureteric reimplantation Bilateral ureteric reimplantation Right nephrectomy
G, grade; STING, subureteric Teflon injection.
normal US had also normal MCUG and DMSA. If an MCUG was performed only in those patients with abnormal DMSA we would have reduced the number of cystograms by 89%. One objection to this strategy could be that it would have resulted in failing to diagnose an appreciable number of infants with reflux but normal DMSA, a finding that may affect further management in terms of chemoprophylaxis. But VUR in this group was mainly non-dilating, and several authors have shown that prophylaxis among patients with low-grade VUR (IeIII) does not decrease the overall incidence of recurrent UTI or the formation of renal scars; moreover, it has been showed that the rate of low-grade VUR resolution does not differ significantly between groups with or without the use of prophylaxis [14e16]. Hence the need for an MCUG in these cases would be guided by the clinicians’ intention to treat the VUR if demonstrated. In Group A, 55% of the infants with scarred kidneys showed non-dilating VUR; they were treated conservatively with monitoring and prophylaxis which was stopped on discharge once toilet trained. Did they benefit from a cystogram? It seems reasonable to question the need to search for VUR in those infants with a non-dilated urinary system on US. In Group B nearly half of the infants with scarred kidney did not show VUR, but interestingly a large number of infants (73%) with non-scarred kidneys had dilating reflux. From this finding it seems reasonable to perform an MCUG in patients with US evidence of upper tract dilatation; in fact, gross hydroureteronephrosis on renal US (the most common finding in Group B) is usually associated with higher grades of VUR which have a lower resolution rate, need close monitoring and are a relative indication for surgery if severe, non-resolving and/or associated with new scarring and recurrent pyelonephritic illnesses. An MCUG is not recommended by NICE in cases of a first UTI responding well within 48 h of treatment, but only in instances of atypical or recurrent UTI or abnormal US [9]. This is in accord with our view of performing an MCUG in infants if hydronephrosis is present on US. We recognize that performing an MCUG only in infants with an abnormal US or scarring on DMSA would have left a subset of 48/354 children from Group A who arguably would not have had their VUR diagnosed. However, the authors argue that the VUR is low grade and, in the absence of anatomical abnormality or evidence of scarring on DMSA, unlikely to be of significance. Recurrent febrile UTIs in this
group, however, may warrant an MCUG as this may then influence/change their management. According to the NICE guidelines, a DMSA scan 4e6 months after the acute infection should be performed for children younger than 3 years with atypical and/or recurrent UTI. Our data support performing a DMSA a few months after the acute infection to detect renal parenchymal damage. Blood pressure and proteinuria should be monitored for children with scars. In our institute, a DMSA scan is performed at a minimum of 3 months following the febrile UTI. Whilst there may be an argument for performing a DMSA scan in the acute phase of the illness to determine the susceptibility of the infant’s kidneys, in our institute this is not practically feasible and hence has not been considered. Photopenic areas on the acute-phase DMSA could in fact ‘screen’ infants who need further imaging and we agree that a prospective study is necessary to explore this further. Finally, the recent NICE guidelines recommend US for infants with first-time UTI that is responsive to treatment within 6 weeks of the infection or during the acute infection if the infection is recurrent or caused by an atypical micro-organism. This selective approach is in accord with recent studies which questioned the limited benefit of routine US for all cases of infantile UTI, particularly for those infants who had a normal prenatal US [17,18]. However, we believe that US has still a valuable role to play after a first febrile infantile UTI. In our population, all infants had in fact normal renal tracts on prenatal US but 17% (Group B: 73/427 infants) had renal system dilatation on US following the first UTI. While this may seem to be a higher percentage than expected, the authors speculate that this may represent a degree of referral bias to our institute which is a tertiary referral centre. One of the concerns that may be voiced over our management strategy is the potential to miss bladder outlet obstruction in male infants e PUV. However, with the presence of specialist paediatric radiologists, advances in ultrasound resolution, and a low surgical threshold to perform a cystourethroscopy in those male infants with even the slightest hint of a bladder outlet pathology, this has not been encountered in this study. With a 10-year retrospective imaging study, the authors appreciate that there may be variability in the readings and reporting. We have not accounted for inter-observer variability among the radiologists or intra-observer variability
152 for the same radiologist, but all radiologists in our institute are specialist paediatric radiologists.
Conclusions In our study, VUR correlated poorly with renal damage in infants hospitalized with UTI. We recommend US and DMSA in all infants <1 year of age following a first febrile UTI. Where the US is normal, MCUG should be reserved for those cases where there is scarring on DMSA and if surgical/medical intervention is contemplated for the VUR if demonstrated. Where the US is abnormal, MCUG should be performed irrespective of findings on the DMSA scan. A randomized prospective study is necessary to assess the outcomes of infants with a first febrile UTI who have diagnostic imaging for specific indications as against routine diagnostic imaging of all such infants.
Conflict of interest statement All authors confirm that they do not have any financial or personal relationship with other people or organizations that could influence this work and hence there is no conflict of interest.
Funding source No funding source.
Ethical approval Approved by the institutional ethics and clinical effectiveness committee at the Sheffield Children’s Hospital.
References [1] Goonasekera CDA, Dillon MJ. Reflux nephropathy and hypertension. J Hum Hypertens 1998;12:497e504. [2] Jacobson SH, Eklof O, Eriksson CG, et al. Development of hypertension and uremia after pyelonephritis in childhood: 27 years of follow up. BMJ 1989;299:703e6. [3] Jungers P, Houillier P, Chauveau D, et al. Pregnancy in women with reflux nephropathy. Kidney Int 1996;50:593e9.
G. Soccorso et al. [4] Report of a Working Group of the Research Unit Royal College of Physicians. Guidelines for the management of acute urinary tract infection in childhood. J R Coll Physicians Lond 1991;25: 36e42. [5] American Academy of Pediatrics Committee on Quality Improvement Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Paediatrics 1999;103:843e52. [6] MacKenzie JR. A review of renal scarring in children. Nucl Med Commun 1996;17:176e90. Review. [7] Hansson S, Dhamey M, Sigstrom O, et al. Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol 2004;172:1071e3. [8] Mahant S, To T, Friedman J. Timing of voiding cystourethrogram in the investigation of urinary tract infections in children. J Pediatr 2001;139:568e71. [9] National Institute for Health and Clinical Excellence. Urinary tract infection in children. Available from:. London: NICE. Available from: http://guidance.nice.org.uk/CG054; 2007. [10] Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985;15:105e9. [11] Westwood ME, Whiting PF, Cooper J, et al. Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review. BMC Pediatr 2005;5:2. [12] Hellstrom M, Jacobsson B. Diagnosis of vesico-ureteric reflux. Acta Paediatr 1999;431(Suppl.):3e12. [13] Rushton HG. The evaluation of acute pyelonephritis and renal scarring with technetium 99 m-dimercaptosuccinic acid renal scintigraphy: evolving concepts and future directions. Pediatr Nephrol 1997;11:108e20. [14] Garin EH, Olavarria F, Nieto VG, et al. Clinical significance of primary vesicoureteral reflux and urinary antibiotics prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Paediatrics 2006;117:626e32. [15] Reddy PP, Evans MT, Hughes PA. Antimicrobial prophylaxis in children with vesico-ureteral reflux: a randomised prospective study of continuous therapy vs intermittent therapy vs surveillance. Pediatrics 1997;100:555e6. [16] Wheeler D, Vimalachandra D, Hodson E, et al. Antibiotics and surgery for vesicoureteric reflux: a meta-analysis of randomised controlled trials. Arch Dis Child 2003;88:688e94. [17] Zamir G, Sakran W, Horowitz Y, Koren A, Miron D. Urinary tract infection: is there a need for routine renal ultrasonography? Arch Dis Child 2004;89:466e8. [18] Montini G, Zucchetta P, Tomasi L, et al. Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1. Pediatrics 2009;123:e239e46.
Investigating febrile UTI in infants: Is a cystogram necessary? G. Soccorso a, J. Wagstaff a, K. Blakey a, G.D. Moss b, P. Broadley c, J.P. Roberts a, P. Godbole a,* a
Department of Paediatric Urology, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK Department of Medicine, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK c Department of Radiology, Sheffield Children’s NHS Foundation Trust, Sheffield S10 2TH, UK b
Received 22 March 2009; accepted 16 June 2009 Available online 19 July 2009
KEYWORDS Infantile UTI; VUR; MCUG; DMSA
Abstract Objective: Current imaging recommendations for investigating any infantile febrile urinary tract infection (UTI) are ultrasound scan (US), micturating cystourethrogram (MCUG) and dimercaptosuccinic acid (DMSA) scan. The aim of this retrospective cohort study was to determine the need and indications for MCUG in the investigation of a first febrile infantile UTI, as doubts have been raised over its benefit. Patients and methods: Information on 427 infants who had undergone US, MCUG and DMSA following a first febrile UTI was prospectively recorded. The infants were divided into two groups: A (354) with normal renal US and B (73) with abnormal US. DMSA findings were correlated with findings on MCUG. Main outcome measures were incidence of recurrent UTIs, change in management or intervention as a result of MCUG, and outcome at discharge. Results: Only 21/354 (6%) infants in Group A had both scarring on DMSA and vesicoureteric reflux (VUR), predominantly low-grade on MCUG. In Group B (abnormal US), 23/73 (32%) had scarring on DMSA and vesicoureteric reflux, predominantly high grade on MCUG. Of the infants with non-scarred kidneys, 73% had dilating reflux. Successful conservative treatment was performed in 423 infants, and 4 infants in Group B required surgery. Conclusion: We recommend US and DMSA in all infantile febrile UTI cases. Where US is normal, MCUG should be reserved for those cases with abnormal DMSA. Where US is abnormal, MCUG should be performed irrespective of findings on DMSA scan. A randomized prospective study is necessary to evaluate this further. ª 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
Introduction
* Corresponding author. E-mail address: [email protected] (P. Godbole).
Febrile UTI is a common problem seen by paediatricians, the urinary tract being the second most common site of infection in infants and children after the respiratory tract.
1477-5131/$36 ª 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jpurol.2009.06.009
Febrile UTI in infants Diagnosis and treatment of UTI are particularly important in infants, given the long-term associations, such as renal scarring, hypertension, chronic renal failure and problems associated with pregnancy [1e3]. Imaging protocols in an infant with a first febrile UTI continue to be a subject of debate. The current practice guidelines of the Royal College of Physicians of London (1991) [4] and of the American Academy of Pediatrics (AAP) (1999) [5] recommend renal US during the acute phase, MCUG several weeks after the infection to identify VUR or obstructive lesions, and a renal DMSA scan at a minimum of 3 months after the infection to rule out renal scarring. The role of MCUG is controversial. Several authors have raised doubts over the benefit of an MCUG in the investigation of a first UTI in children aged less than 1 year of age [6e8]. In the UK, The National Institute of Clinical Excellence (NICE) produced recent guidelines to improve and make more cost effective the diagnosis, treatment and further management of UTI in childhood [9]. The recommendations are complex, dividing children into different age groups and UTIs into different variants, combinations of which determine the type and timing of subsequent imaging studies. We conducted a 10-year retrospective review of infants presenting with a febrile pyelonephritic illness to a tertiary paediatric hospital to specifically investigate the role of MCUG in these infants. Analysing our data, we suggest a diagnostic protocol correlating it with the recent NICE guidelines.
Methods All infants under 1 year of age presenting with a febrile UTI were admitted under the care of paediatricians. At our institution, the current practice is for all infants presenting with a febrile UTI to be admitted for intravenous antibiotics with subsequent chemoprophylaxis till investigations are complete. These infants have an ultrasound (US) scan during this admission. Subsequently, all infants have an MCUG and DMSA scan, the DMSA scan being at least 3 months following the last infection. Where the acute US scan shows evidence of bladder outlet obstruction, this is confirmed by MCUG and managed accordingly. Those infants under 1 year of age referred by their primary care practitioner with a history of a febrile UTI are investigated along the same lines with US, MCUG and DMSA. The imaging data for these infants was prospectively recorded on a radiology database. Case notes of all infants from the database between 1996 and 2006 were available for review. A febrile UTI was defined as pyrexia >38 C associated with culture-proven pure growth of an organism (>105 colony-forming units/high-power field) from an appropriately collected urine sample. The sample was collected as a clean-catch midstream urine sample. Where this was not possible, a suprapubic aspirate with US control was utilized to obtain a sample. The US examination was considered normal in the case of bilateral normal kidneys, with no evidence of hydroureteronephrosis or bladder abnormality. The VUR on MCUG was graded according to the international VUR classification [10]. DMSA was considered normal if uptake of radioisotope was homogenous with no evidence of scarring and relative uptake within normal range.
149 Six paediatric radiologists reported individual imaging studies and were blinded to the reports of other studies for the same infant. A total of 427 infants, 258 boys (60%) and 169 girls (40%) with a median age of 5.2 months (0e12) were eligible for enrolment. The infants were divided in two groups: normal renal US (Group A Z 354 infants/708 renal units) and abnormal US (Group B Z 73 infants/146 renal units). For both groups, DMSA findings were correlated with findings on MCUG. Main outcome measures evaluated were incidence of recurrent UTIs, change in management or intervention as a result of the MCUG, and outcome at discharge. Institutional ethics and clinical effectiveness committee approval was obtained for this study.
Results All infants had a proven febrile UTI: the most common organism isolated was Escherichia coli (67%) followed by Enterobacter (21%) and Enterococcus (8%). Klebsiella was isolated from 3.5% of the infants and Staphylococcus aureus in only 0.5%.
Group A: normal US In Group A (Fig. 1) (n Z 354), there were 142 girls (40%) and 212 boys (60%). The average age was 4.5 months (range 0.3e12 months). Scarring on DMSA scan was found in 38/354 (11%). Of these, 21/38 (55%) had VUR on MCUG. Hence, 21/ 354 (6%) infants had both VUR and scarring on DMSA. The VUR was predominantly low grade. Of the 354 infants, 316 (89%) had a normal DMSA scan. Of these, 48/316 (15%) had low-grade VUR on MCUG. Overall, VUR was present in 69 infants (19%): 38 were male and 31 female; VUR was predominantly of low grade, unilateral in 37 and bilateral in 32 infants, making a total of 101 refluxing renal units. All infants of Group A were successfully treated conservatively by the medical team with prophylactic antibiotics, regular follow up and renal function/blood pressure monitoring as indicated. Those with normal investigations were discharged and chemoprophylaxis was discontinued. There was no further occurrence of UTI in infants in Group A during the period of observation. All were normotensive at discharge and on no medication.
Group B: normal US Seventy-three infants (Fig. 2) (average age 3.9 months, range 0.2e12 months), 46 boys (63%) and 27 girls (37%), showed abnormal findings on US. In 27 cases (37%) both renal units were abnormal. The most common findings were moderate to severe hydroureteronephrosis and duplex system. Forty-three infants (59%) revealed scarring on DMSA scan and 23/43 (53%) demonstrated VUR on MCUG. The majority of infants (73%) without scarring on DMSA scan showed VUR on cystogram. Overall, VUR was present in 45/73 infants (62%), 29 male and 16 female, for a total of 66 renal units, and was grade IIeV. Of the 73 infants with an abnormal US, 23 had scarring on DMSA and VUR on MCUG (32%).
150
G. Soccorso et al.
Fig. 1
Group A: results of imaging studies.
The same conservative strategy (monitoring and prophylaxis) used for Group A was applied successfully by the medical team in the majority of the children of Group B. Breakthrough UTI rate was 12% (9/73). Eight children presented with one episode of cystitis. Only one child presented with further pyelonephritis. These episodes were diagnosed on clinical and radiological grounds. All nine continued with the conservative treatment. Infants with VUR or scars on DMSA continued on prophylaxis until they were potty trained, and remained under appropriate follow up for monitoring of blood pressure and renal function where indicated. Only four children in Group B (5%) required surgical intervention (Table 1). Patients 1 and 4 had a right heminephrectomy and right nephrectomy, respectively, for a non-functioning upper moiety of a right duplex (Patient 1) and a poorly functioning kidney (Patient 4). Patients 2 and 3 had bilateral ureteric reimplantation in view of their recurrent episodes of urinary sepsis.
Discussion In this study, we reviewed our practice with the aim of simplifying the routine imaging protocols for infantile UTI suggested by the Royal College of Physicians and the AAP. Their recommendations are not based on firm evidence [11].
Fig. 2
The authors appreciate that the AAP 1999 guidelines recommend imaging for infants between the age of 2 months and 2 years. However, in our institute, the Royal College of Physicians guidelines 1991 have been followed and this study is based on infants treated accordingly. US is the routine, simple, non-invasive method of investigation for a child with UTI. Modern US is very sensitive in the assessment of the gross anatomy of the urinary tract, demonstrating dilatation of ureters, hydronephrosis, renal shapes, duplications, ureteroceles, and horseshoe kidney. In our study, US showing dilatation of the urinary tract correlated well with VUR grade IIIeV on MCUG. This was particularly evident in the infants of Group B; 19% of the infants in Group A had reflux but this was mainly nondilating on cystogram and none was of grade IV or V. As previously reported in other studies, we found a poor correlation between VUR demonstrated on MCUG and renal scarring on DMSA; in fact, 45% of infants with scarred kidneys in Group A and 47% in Group B did not show reflux on cystogram. This could be explained by the fact that reflux is often intermittent or that it is not a prerequisite for renal damage [12,13]. It has been suggested that MCUG contributes little to the management of infantile UTI in the context of normal US and DMSA [7]. In Group A the majority of infants (76%) with
Group B: results of imaging studies.
Febrile UTI in infants Table 1
151
Patients from Group B who required surgical treatment.
No.
US
MCUG
DMSA
Surgery
1
Right duplex with hydronephrosis and ureterocele Right hydroureteronephrosis with right scarring Bilateral hydroureteronephrosis with hypertrophic bladder Right hydroureter Left hydronephrosis
Right GIII VUR Ureterocele
Right duplex with non-functioning upper pole Left lower pole scar Bilateral scarring
Right heminephrectomy
2 3 4
Bilateral VUR Right GIV Left GIII ***Bilateral VUR Right GV Left GIII Bilateral GIII VUR
Bilateral scarring Function right kidney 6% Left lower pole scar
STING unsuccessful Bilateral ureteric reimplantation Bilateral ureteric reimplantation Right nephrectomy
G, grade; STING, subureteric Teflon injection.
normal US had also normal MCUG and DMSA. If an MCUG was performed only in those patients with abnormal DMSA we would have reduced the number of cystograms by 89%. One objection to this strategy could be that it would have resulted in failing to diagnose an appreciable number of infants with reflux but normal DMSA, a finding that may affect further management in terms of chemoprophylaxis. But VUR in this group was mainly non-dilating, and several authors have shown that prophylaxis among patients with low-grade VUR (IeIII) does not decrease the overall incidence of recurrent UTI or the formation of renal scars; moreover, it has been showed that the rate of low-grade VUR resolution does not differ significantly between groups with or without the use of prophylaxis [14e16]. Hence the need for an MCUG in these cases would be guided by the clinicians’ intention to treat the VUR if demonstrated. In Group A, 55% of the infants with scarred kidneys showed non-dilating VUR; they were treated conservatively with monitoring and prophylaxis which was stopped on discharge once toilet trained. Did they benefit from a cystogram? It seems reasonable to question the need to search for VUR in those infants with a non-dilated urinary system on US. In Group B nearly half of the infants with scarred kidney did not show VUR, but interestingly a large number of infants (73%) with non-scarred kidneys had dilating reflux. From this finding it seems reasonable to perform an MCUG in patients with US evidence of upper tract dilatation; in fact, gross hydroureteronephrosis on renal US (the most common finding in Group B) is usually associated with higher grades of VUR which have a lower resolution rate, need close monitoring and are a relative indication for surgery if severe, non-resolving and/or associated with new scarring and recurrent pyelonephritic illnesses. An MCUG is not recommended by NICE in cases of a first UTI responding well within 48 h of treatment, but only in instances of atypical or recurrent UTI or abnormal US [9]. This is in accord with our view of performing an MCUG in infants if hydronephrosis is present on US. We recognize that performing an MCUG only in infants with an abnormal US or scarring on DMSA would have left a subset of 48/354 children from Group A who arguably would not have had their VUR diagnosed. However, the authors argue that the VUR is low grade and, in the absence of anatomical abnormality or evidence of scarring on DMSA, unlikely to be of significance. Recurrent febrile UTIs in this
group, however, may warrant an MCUG as this may then influence/change their management. According to the NICE guidelines, a DMSA scan 4e6 months after the acute infection should be performed for children younger than 3 years with atypical and/or recurrent UTI. Our data support performing a DMSA a few months after the acute infection to detect renal parenchymal damage. Blood pressure and proteinuria should be monitored for children with scars. In our institute, a DMSA scan is performed at a minimum of 3 months following the febrile UTI. Whilst there may be an argument for performing a DMSA scan in the acute phase of the illness to determine the susceptibility of the infant’s kidneys, in our institute this is not practically feasible and hence has not been considered. Photopenic areas on the acute-phase DMSA could in fact ‘screen’ infants who need further imaging and we agree that a prospective study is necessary to explore this further. Finally, the recent NICE guidelines recommend US for infants with first-time UTI that is responsive to treatment within 6 weeks of the infection or during the acute infection if the infection is recurrent or caused by an atypical micro-organism. This selective approach is in accord with recent studies which questioned the limited benefit of routine US for all cases of infantile UTI, particularly for those infants who had a normal prenatal US [17,18]. However, we believe that US has still a valuable role to play after a first febrile infantile UTI. In our population, all infants had in fact normal renal tracts on prenatal US but 17% (Group B: 73/427 infants) had renal system dilatation on US following the first UTI. While this may seem to be a higher percentage than expected, the authors speculate that this may represent a degree of referral bias to our institute which is a tertiary referral centre. One of the concerns that may be voiced over our management strategy is the potential to miss bladder outlet obstruction in male infants e PUV. However, with the presence of specialist paediatric radiologists, advances in ultrasound resolution, and a low surgical threshold to perform a cystourethroscopy in those male infants with even the slightest hint of a bladder outlet pathology, this has not been encountered in this study. With a 10-year retrospective imaging study, the authors appreciate that there may be variability in the readings and reporting. We have not accounted for inter-observer variability among the radiologists or intra-observer variability
152 for the same radiologist, but all radiologists in our institute are specialist paediatric radiologists.
Conclusions In our study, VUR correlated poorly with renal damage in infants hospitalized with UTI. We recommend US and DMSA in all infants <1 year of age following a first febrile UTI. Where the US is normal, MCUG should be reserved for those cases where there is scarring on DMSA and if surgical/medical intervention is contemplated for the VUR if demonstrated. Where the US is abnormal, MCUG should be performed irrespective of findings on the DMSA scan. A randomized prospective study is necessary to assess the outcomes of infants with a first febrile UTI who have diagnostic imaging for specific indications as against routine diagnostic imaging of all such infants.
Conflict of interest statement All authors confirm that they do not have any financial or personal relationship with other people or organizations that could influence this work and hence there is no conflict of interest.
Funding source No funding source.
Ethical approval Approved by the institutional ethics and clinical effectiveness committee at the Sheffield Children’s Hospital.
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